Publications by authors named "Sjoerd Aertssen"
Tankyrase 1 and 2 (TNKS1/2) catalyze post-translational modification by poly-ADP-ribosylation of a plethora of target proteins. In this function, TNKS1/2 also impact the WNT/β-catenin and Hippo signaling pathways that are involved in numerous human disease conditions including cancer. Targeting TNKS1/2 with small-molecule inhibitors shows promising potential to modulate the involved pathways, thereby potentiating disease intervention.
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- Tankyrases 1 and 2 are key targets in WNT/β-catenin and Hippo signaling pathways, and the researchers focused on optimizing inhibitors previously developed with a specific triazole structure.
- A systematic lead optimization process involved changing side groups on the inhibitor while keeping the main structure intact, leading to a new series of compounds with significantly improved target inhibition.
- The optimized compounds demonstrated better solubility, efficacy, and favorable absorption properties, making them potentially effective treatments for colon cancer.
A concise and efficient synthesis of cyclopentitols as a scaffold for a two-dimensional compound library for drug discovery is described. Starting from d-mannose, the key steps are Wittig olefination and ring-closing metathesis (RCM) followed by a [3,3]-sigmatropic Overmann rearrangement to form an sp(3)-rich, natural product-like scaffold from which a focused compound library with different functionalities is prepared.
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